The Golgi complex is an organelle responsible for receiving synthesized cargo from the endoplasmic reticulum for subsequent post-translations modifications, sorting and secretion. A family of proteins named Golgi Reassembly and Stacking Proteins (GRASP) is essential for the correct assembly and laterally tethering of the Golgi cisternae, a necessary structuration to keep this organelle working correctly. The GRASP structure is mainly composed of two regions: an N-terminal formed by two PDZ domains connected by a short loop (GRASP domain) and a non-conserved C-terminal region, rich in serine and proline residues. Although there are now a few crystal structures solved for the N-terminal domain, it is surprising to notice that no information is currently available regarding a full-length protein or even about dynamic and structural differences between the two PDZs in solution, which is the main functional region of this protein. Using a full-length GRASP model, we were capable of detecting the coexistence of regular secondary structures and large amounts of disordered regions. The overall structure is less compact than a regular globular protein and the high structural flexibility makes its hydrophobic core more accessible to solvent. GRASP coexist in a dynamic conformational ensemble of a µs-ms timescale. Our results indicate an unusual behavior of GRASP in solution, closely resembling a class of collapsed intrinsically disordered proteins called molten globule. We report here also the disorder-to-order transition propensities for a native molten globule-like protein in the presence of different mimetics of cell conditions. Changes in the dielectric constant (such as those experienced close to the membrane surface) seem to be the major factor capable of inducing several disorder-to-order transitions in GRASP, which seems to show very distinct behavior when in conditions that mimic the vicinity of the membrane surface as compared to those found when free in solution. Other folding factors such as molecular crowding, counter ions, pH and phosphorylation exhibit lower or no effect on GRASP secondary structure and/or stability. This is the first study focusing on understanding the disorder-to-order transitions of a molten globule structure without the need for any mild denaturing condition. Regarding the PDZs that form the GRASP domain, we observed that GRASPs are formed by a more unstable and flexible PDZ1 and much more stable and structurally well-behaved PDZ2. More than that, many of the unstable regions found in PDZ1 are in the predicted binding pocket, suggesting a structural promiscuity inside this domain that correlates with the functional promiscuity of interacting with multiple protein partners. This thesis presents the first structural characterization of a full-length GRASP, the first model of how GRASPs (or any molten globule-like protein) can be modulated by the cell during different cell functionalities and the first work in the community proving that the established idea that both PDZs are structurally equivalent is not completely right / O complexo de Golgi é um organela responsável pela recepção de carga sintetizada no retículo endoplasmático e por subsequente modificações pós-traducionais, classificação e secreção. Uma família de proteínas chamada Golgi Reassembly and Stacking Proteins (GRASP) é essencial para o correto empilhamento das cisternas e conexões laterais das pilhas do complexo de Golgi, uma estruturação necessária para manter essa organela funcionando corretamente. A estrutura das GRASPs é composta de duas regiões principais: uma extensão N-terminal formado por dois domínios PDZ conectados por um loop (domínio GRASP) e uma região C-terminal não conservada, rica em resíduos de serina e prolina. Embora existam algumas estruturas cristalográficas resolvidas para o domínio N-terminal, é surpreendente notar que não havia nenhuma informação na literatura sobre a construção inteira de um GRASP, ou mesmo um estudo detalhado sobre os PDZs no N-terminal em solução, que é a principal região funcional dessa proteína. Usando um modelo de GRASP em sua construção completa, fomos capazes de detectar a coexistência de estruturas secundárias regulares e grandes quantidades de regiões desordenadas. A estrutura é menos compacta do que uma proteína globular e a alta flexibilidade estrutural torna o seu núcleo hidrofóbico mais acessível ao solvente. GRASPs coexistem em um conjunto conformacional dinâmico numa escala de tempo característico de s-ms. Nossos resultados indicam um comportamento incomum da GRASP em solução, similar à de uma classe de proteínas intrinsicamente desordenadas colapsadas conhecidas como glóbulos fundidos. Nós relatamos também as propensões de transição estrutural do tipo desordem-ordem para uma proteína glóbulo fundido nativa, induzidas pela presença de diferentes miméticos de condições celulares especificas. A mudança na constante dielétrica do meio (como as experimentadas próximas à superfície da membrana biológica) é o principal modulador estrutural, capaz de induzir múltiplas transições desordem-ordem na GRASP, sugerindo um comportamento muito distinto quando em condições que imitam a vizinhança da superfície da membrana em comparação com os encontrados quando livre em solução. Outros fatores de enovelamento, tais como o molecular crowding, contra-ions, pH e a fosforilação exibem efeitos menores (ou nenhum) na estrutura secundária e/ou estabilidade da GRASP. Este é o primeiro estudo focado na compreensão das transições desordem-ordem em uma estrutura do tipo glóbulo fundido sem que houvesse a necessidade de qualquer condição desnaturante. Em relação aos PDZs que formam o domínio GRASP, observamos que as GRASPs são formadas por um PDZ1 mais instável e flexível e um PDZ2 muito mais estável e estruturalmente bem comportado. Mais do que isso, muitas das regiões instáveis encontradas no PDZ1 estão no predito bolsão de ligação, sugerindo uma promiscuidade estrutural dentro desse domínio que se correlaciona com a promiscuidade funcional de interação com múltiplos parceiros proteicos. É apresentado nesta tese a primeira caracterização estrutural de uma GRASP em sua forma completa, o primeiro modelo de como as GRASPs (ou qualquer proteína em forma de glóbulo fundido) pode ser modulada estruturalmente pela célula durante diferentes funcionalidades e o primeiro trabalho na comunidade provando que a estabelecido ideia de que ambos os PDZs são estruturalmente equivalentes não é completamente correta

Orientadores: André Luiz Morelato França, Paulo Morelato França / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-20T08:47:23Z (GMT). No. of bitstreams: 1 Usberti_FabioLuiz_D.pdf: 2207082 bytes, checksum: 83078a448a40f75c373b989f9af006fb (MD5) Previous issue date: 2012 / Resumo:O problema de roteamento em arcos capacitado e aberto (open capacitated arc routing problem, OCARP) é um problema de otimização combinatorial NP-difícil em que, dado um grafo não-direcionado, o objetivo consiste em encontrar um conjunto de rotas de custo mínimo para veículos com capacidade restrita que atendam a demanda de um subconjunto de arestas. O OCARP está relacionado com o problema de roteamento em arcos capacitado (capacitated arc routing problem, CARP), mas difere deste pois o OCARP não possui um nó depósito e as rotas não estão restritas a ciclos. Aplicações da literatura para o OCARP são discutidas. Uma formula ção de programação linear inteira é fornecida junto com propriedades do problema. Uma metaheurística GRASP (greedy randomized adaptive search procedure) com reconexão por caminhos (path-relinking) é proposta e comparada com outras metaheurísticas bem-sucedidas da literatura. Algumas características do GRASP são: (i) ajuste reativo de parâmetros, cujos valores são estocasticamente selecionados com viés 'aqueles valores que produziram, em média, as melhores soluções; (ii) um filtro estatístico que descarta soluções iniciais caso estas tenham baixa probabilidade de superar a melhor solução incumbente; (iii) uma busca local infactível que gera soluções de baixo custo utilizadas para explorar fronteiras factíveis/infactíveis do espaço de soluções; (iv) a reconexão por caminhos evolutiva aprimora progressivamente um conjunto de soluções de elevada qualidade (soluções elites). Testes computacionais foram conduzidos com instâncias CARP e OCARP e os resultados mostram que o GRASP é bastante competitivo, atingindo os melhores desvios entre os custos das soluções e limitantes inferiores conhecidos. Este trabalho também propõe um algoritmo exato para o OCARP que se baseia no paradigma branch-and-bound. Três limitantes inferiores são propostos e um deles utiliza o método dos subgradientes para resolver uma relaxação lagrangeana. Testes computacionais comparam o algoritmo branch-and-bound com o CPLEX resolvendo um modelo reduzido OCARP de programa ção linear inteira. Os resultados revelam que o algoritmo branch-and-bound apresentou resultados melhores que o CPLEX no que diz respeito aos desvios entre limitantes e ao número de melhores soluções / Abstract: The Open Capacitated Arc Routing Problem (OCARP) is an NP-hard combinatorial optimization problem where, given an undirected graph, the objective is to find a minimum cost set of tours that services a subset of edges with positive demand under capacity constraints. This problem is related to the Capacitated Arc Routing Problem (CARP) but differs from it since OCARP does not consider a depot, and tours are not constrained to form cycles. Applications to OCARP from literature are discussed. An integer linear programming formulation is given, followed by some properties of the problem. A Greedy Randomized Adaptive Search Procedure (GRASP) with path-relinking (PR) solution method is proposed and compared with other successful metaheuristics. Some features of this GRASP with PR are (i) reactive parameter tuning, where the metaheuristic parameters values are stochastically selected biased in favor of those values which produced the best solutions in average; (ii) a statistical filter, which discards initial solutions if they are unlikely to improve the incumbent best solution; (iii) infeasible local search, where high-quality solutions, though infeasible, are used to explore the feasible/infeasible boundaries of the solution space; (iv) evolutionary PR, a recent trend in which a pool of elite solutions is progressively improved by relinking pairs of elite solutions. Computational tests were conducted for both CARP and OCARP instances, and results reveal that the GRASP with PR is very competitive, achieving the best overall deviation from lower bounds. This work also proposes an exact algorithm for OCARP, based on the branch-and-bound paradigm. Three lower bounds are proposed, one of them uses a subgradient method to solve a Lagrangian relaxation. The computational tests compared the proposed branch-and-bound with a commercial state-of-the-art ILP solver. Results reveal that the branch-and-bound outperformed CPLEX in the overall average deviation from lower bounds / Doutorado / Automação / Doutor em Engenharia Elétrica

Afin d’améliorer la qualité de prédiction des techniques de classification automatique et de fouilles de données, plusieurs modèles ont été proposés dans la littérature en vue d’extraire des connaissances à partir des données. Toutefois, avec l’expansion des systèmes d’information et des technologies associées, ces techniques d’apprentissage s’avèrent de moins en moins adaptées aux nouvelles tailles et dimensions des données. On s’intéresse dans cette étude aux problèmes de grande dimensionnalité et à l’amélioration du processus d’apprentissage des méthodes de classification à travers les techniques de filtrage et de sélection d’attributs. Le problème « d’identification d’attributs pertinents » (Feature Selection Problem), tel qu’il est défini dans la littérature, relève d’une nature combinatoire. Dans le cadre de cette thèse, on s’est intéressé au développement de nouvelles techniques d’optimisation approchées et spécifiques au problème traité ainsi qu’à l’amélioration d’algorithmes existants. La conception, l’implémentation et l’étude empirique ont montré l’efficacité et la pertinence des métaheuristiques proposées. / Although the expansion of storage technologies, networking systems, and information system methodologies, the capabilities of conventional data processing techniques remain limited. The need to knowledge extraction, compact representation and data analysis are highly motivated by data expansion. Nevertheless, learning from data might be a complex task, particularly when it includes noisy, redundant and information-less attributes. Feature Selection (FS) tries to select the most relevant attributes from raw data, and hence guides the construction of final classification models or decision support systems. Selected features should be representative of the underlying data and provide effective usefulness to the targeted learning paradigm (i.e. classification). In this thesis, we investigate different optimization paradigms as well as its adaptation to the requirements of the feature selection challenges, namely the problem combinatorial nature. Both theoritical and empirical aspects were studied, and confirm the effectiveness of the adopted methodology as well as the proposed metaheuristic based approaches.

Master of Science / Department of Computing and Information Sciences / David A. Gustafson / Octant analysis, when combined with properties of the multivariate central limit theorem and multivariate normal distribution, allows finding a reasonable grasping point on an unknown novel object possible. This thesis’s original contribution is the ability to find progressively improving grasp points in a poor and/or sparse point cloud. It is shown how octant analysis was implemented using common consumer grade electronics to demonstrate the applicability to home and office robotics. Tests were carried out on three novel objects in multiple poses to determine the algorithm’s consistency and effectiveness at finding a grasp point on those objects. Results from the experiments bolster the idea that the application of octant analysis to the grasping point problem seems promising and deserving of further investigation. Other applications of the technique are also briefly considered.

One of the significant side-effects of growing urbanization is the constantly increasing amount of freight transportation in cities. This is mainly performed by conventional vans and trucks and causes a variety of problems such as road congestion, noise nuisance and pollution. Yet delivering goods to residents is a necessity. Sustainable concepts of city distribution networks are one way of mitigating difficulties of freight services. In this paper we develop a two-echelon city distribution scheme with temporal and spatial synchronization between cargo bikes and vans. The resulting heuristic is based on a greedy randomized adaptive search procedure with path relinking. In our computational experiments we use artificial data as well as real-world data of the city of Vienna. Furthermore we compare three distribution policies. The results show the costs caused by temporal synchronization and can give companies decision-support in planning a sustainable city distribution concept.

[pt] GRASP (Greedy Randomized Adaptive Search Procedure)é uma metaeurística de partidas múltiplas usada para obter soluções para problemas de otimização combinatória. Nesse trabalho. A metaheurística GRASP tem sido usada para obter soluções de qualidade para muitos problemas de otimização combinatória. Nesse trabalho é proposta uma metodologia para análise do comportamento da metaheurística GRASP. Também são propostas estratégias de hibridização com o religamento de caminhos. Essas estratégias foram desenvolvidas para o problema de atribuição de três índices (AP3) e para o problema de escalonamento de tarefas conhecido na literatura como job-shop schedulling problem (JSP) e são analisadas de acordo com a metodologia proposta. A metodologia para análise do comportamento do método GRASP pode ser usada para prever a partir da versão seqüencial do algoritmo, como a qualidade da solução do algoritmo implementado em paralelo irá variar. Os algoritmos GRASPs desenvolvidos para AP3 e para JSP foram paralelizados e os resultados são comparados aos resultados obtidos usando a metodologia proposta. / [en] GRASP (Greedy Randomized Adaptive Search Procedure) is a multi-start metaheuristic for combinatorial optimization problems. GRASP has been used to find quality solutions of several combinatorial optimization problems. In this work we describe a methodology for analysis of GRASP. Hybrid strategies of GRASP with path relinking are also proposed. These strategies are studied for the 3-index assignment problem (AP3) and for the job-shop schedulling problem (JSP) and are analyzed according to the methodology proposed. The methodology for analysis of GRASP is used to predict qualitatively how the quality of the solution varies in a parallel independent GRASP, using the data of the GRASP sequential version as input. The GRASPs for the AP3 and for the JSP are parallelized and the computational results are compared to the results obtained using the methodology proposed.

Orientador: Rubén Augusto Romero Lázaro / Banca: José Roberto Sanches Mantovani / Banca: Walmir de Freitas Filho / Resumo: O Problema do Planejamento da Expansão de Sistemas de Transmissão é um problema de otimização combinatória, cujo objetivo é buscar o atendimento de requisitos de cargas a custos mínimos de investimentos, percebendo um horizonte de longo prazo. A perspectiva do planejamento otimizado deve ser feita observando duas possiblidades: o planejamento estático e o planejamento multiestágio. No planejamento estático, o planjedor procura responder as questões onde e que tipos de elementos de transmissão precisam ser adicionados ou construídos para integrar a solução do sistema futuro. No entanto, quando a estratégia de expansão ótima abrange todo um período, o planejador deseja saber quando o circuito deve ser instalado, trata-se de um planejamento multiestágio. Em ambas alternativas, a resolução do problema do planejamento deve abranger duas etapas consecutivas: a modelagem matemática e a técnica de solução para resolver essa modelagem. Neste trabalho é apresentada uma proposta de planejamento estático utilizando aMetaheurística GRASP como técnica de solução para o problema do planejamento. / Abstract: The Problem of Expansion Planning of Transmission Systems is a combinatorial optimization problem whose goal is to seek the assistance of cargo requirements at minimal cost investment, realizing a long-term horizon.The prospect of planning should be optimized observing two possibilities: planning static and multistage planning. In planning static, designer seeks to answer the questions where and what types of transmission elements need to be added or built to integrate the solution of the future system. However, when the optimal expansion strategy covers the whole period, the planner wants to know when the circuit must be installed, it is a multistage planning. In both alternatives, solving the problem of planning should cover two consecutive steps: mathematical modeling and solution technique to solve this modeling.This work presents a planning proposal using the static technique as GRASP metaheuristic solution to the problem of planning. / Mestre

Estágio orientado na empresa, pelo Eng. Nuno Filipe Correia de Melo Ferreira de Almeida / Tese de mestrado integrado. Engenharia Industrial e Gestão. Faculdade de Engenharia. Universidade do Porto. 2012

The role of digital humans in product design and assessment is ever increasing. Accurate digital human models are used to provide feedback on virtual prototypes of products, thus reducing costs and shortening the design cycle. An essential part of product assessment in the virtual world is the ability of the human model to interact correctly and naturally with the product model. This involves reaching, grasping and manipulation. This work addresses the difficult problem of grasp planning for digital humans. We develop a semi-interactive system for synthesizing grasps based on the object's shape, and implement this system for SantosTM, the digital human developed at the Virtual Soldier Research Program at the University of Iowa. The system is composed of three main parts: First, a shape matching module that creates an initial power grasp for the object based on a database of pre-calculated grasps. Second, an optimization based module provides control of the fingertip locations. This can be used to synthesize precision grasps under the user's guidance. Finally, a grasp quality module provides feedback about the grasp's mechanical stability. The novelty of our approach lies in the fact that it takes into consideration the upper body posture when planning the grasp, so the whole arm and the torso are involved in the grasp.

The application of technology makes a lot of things easier, but for individuals with disability, it makes things possible. Rehabilitation robotics aims at providing robotic devices, which can act as functional extensions of the user, while performing basic activities. Providing a well-designed gripper as its end-effector can greatly enhance the performance of a rehabilitation robot. The gripper performs simple tasks like picking up objects and manipulating objects, which help in performing activities of daily living. This thesis describes the development of a prototype gripper for a wheelchair mounted robot. The pre-development surveys conducted before the development of commercialized robotic assistive devices were analyzed and user task priorities were understood. The role of the gripper as an object-grasping device was focused upon. The size and weight parameters, which the gripper should effectively grasp, were decided. Based on these parameters, a prototype was developed. Force sensors were used to monitor the gripping forces. The data was acquired using a Data Acquisition System. The gripping forces were measured using a Labview program that utilized the force-voltage relationship for the sensor. This relationship was obtained by performing calibration experiments. The performance of the prototype was tested using objects that are used in everyday environment and was analyzed by conducting a set of experiments. A relay circuit was designed that would stop the motors once the gripping forces exceeded a threshold value for a given object. This avoided any damage to the object during the gripping process. The gripping forces measured were found to be in close agreement to the theoretically calculated force values.